Delayed formation of proteoglycan aggregate structures in human articular cartilage disease states

Abstract

Proteoglycans are major components of many extracellular matrices. In cartilage they provide reversible resistance to compression and exist as molecules with MW of 1-3 .times. 106. There is a central protein core of MW approximately 2 .times. 105 with specialized subregions, 1 containing mainly the chondroitin sulfate chains, another most of the keratan sulfate chains and a 3rd is a largely globular structure interacting specifically with both hyaluronic acid and a link protein to form stable aggregate structures such as those identified in human articular cartilage. In embryonic and tissue culture systems, proteoglycans are isolated as aggregate structures in as little as 5-10 min after synthesis (sulfation) with no nonaggregating precursor detected. Heinegard and Hascall characterized the small proportion of nonaggregating proteoglycan present in bovine nasal septum cartilage and found that it contained more peptide than the aggregating proteoglycan. The MW of unprocessed protein core, synthesized by a wheat-germ translating system from chick sternal cartilage mRNA, is .apprx. 340,000, leaving open the possibility of intermediates. The presence, in some human diseased cartilages, of a proteoglycan population that initially will not aggregate with the hyaluronic acid but subsequently can be chased into aggregate, is reported.